A Study of CLR325 in Chronic Stable Heart Failure Patients.

NCT02696967 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CCLR325X22022016-001387-12
• Study Type: interventional
• Target: 26
• Locations: 5 countries
• Sites: 11

Brief Summary

The purpose of this study was to determine the safety and tolerability of CLR325 intravenous (i.v.) infusion in patients with stable heart failure to determine if further clinical development of the drug in this indication was warranted.

Conditions

Chronic Stable Heart Failure

Keywords

Apelin; CLR325; Chronic heart failure

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Adverse Events, Serious Adverse Events and Death

  Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) in each treatment arm to demonstrate that CLR325 is safe for the treatment of chronic stable heart-failure patients through the monitoring of relevant clinical and laboratory safety parameters.

  Day 1 to 28

Secondary Outcomes (12)

• Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to 18 Hours (AUC0-18hr)

  0, 0.5, 3, 5, 8, 10, 12, and 18 hours post start of CLR325 infusion on Day 1

• Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From From Time Zero to 28 Hours (AUC0-28hrs)

  0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

• Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)

  0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

• Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)

  0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

• Pharmacokinetic of CLR325: Clearance From Plasma (CL) Following Drug Administration

  0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1

Study Arms (2)

CLR325

EXPERIMENTAL

Patients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of CLR325 (i.v.) in double blind manner.

Drug: CLR325

Placebo

PLACEBO COMPARATOR

Patients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of placebo (i.v.) in double blind manner.

Other: Placebo

Interventions

CLR325 DRUG

CLR325 Concentrate for solution for infusion

CLR325

Placebo OTHER

Normal saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients \>18 years of age
• Body weight between 50 kg and 140 kg
• Cardiac ejection fraction of ≤ 45% assessed within the last 6 months
• For PA catheter cohorts, patients who are planned to have a clinically indicated pulmonary artery catheter in place prior to randomization
• In the opinion of the investigator, heart failure patients who do not require a change in their dose of acetylcholinesterase (ACE), angiotensin receptor blocker (ARB), β-blocker, mineralocorticoid receptor antagonist, or diuretic for 24 h after randomization.
• At Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) assessment in the supine position after the subject has rested for at least five minutes.

You may not qualify if:

• Impaired renal function as indicated by clinically significant abnormal creatinine values (Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m2 calculated using the Modification of Diet in Renal Disease Study (MDRD) equation)
• History of chronic hepatitis of any non-cardiac etiology
• History of any active or clinically significant cardiac tachyarrhythmia (such as recurrent atrial fibrillation with rapid ventricular response within the last year) and patients with chronic atrial fibrillation with a pulse rate ≤ 100 bpm
• Patients who received an i.v. infusion of a cardiac inotrope (e.g., dobutamine or milrinone) in the last 24 h prior to randomization
• Patients with any significant change in their dose of their ACE, ARB, mineralocorticoid receptor antagonist, diuretic, or β-blocker within the last 12 h
• Patients with known significant valvular heart diseases indicated by the following:
• severe aortic stenosis (aortic valve area \< 1.0 cm2 or peak gradient \> 50 mm Hg as determined by echocardiography)
• severe mitral stenosis
• History of acute coronary syndrome within the last 60 days as determined by both clinical and enzymatic criteria
• For echocardiography-based cohorts only, patients admitted to an inpatient setting for acute decompensated heart failure within the last 30 days
• For PA catheter cohorts, patients with a pulmonary capillary wedge pressure of \<10 mm Hg at Baseline. For echocardiographic cohorts, patients with a lateral E/E' ratio of \< 7 on their baseline echocardiogram. For patients in whom a lateral E/E' ratio cannot be determined (e.g., patients in atrial fibrillation), a central venous pressure of \< 5 mm Hg on baseline echocardiogram as determined by inferior vena cava criteria.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Chicago, Illinois, 60611, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44195, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

Aalst, 9300, Belgium

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Greifswald, 17475, Germany

Location

Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

Location

Novartis Investigative Site

Singapore, 169609, Singapore

Location

Related Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2016
• First Posted: March 2, 2016
• Study Start: May 17, 2016
• Primary Completion: January 14, 2019
• Study Completion: January 14, 2019
• Last Updated: January 5, 2021
• Results First Posted: March 4, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); DE (2); NL (1); SG (1); US (6)